S-Space College of Medicine/School of Medicine (의과대학/대학원) Psychiatry (정신과학전공) Journal Papers (저널논문_정신과학전공)
Membrane depolarization induces the undulating phosphorylation/dephosphorylation of glycogen synthase kinase 3beta, and this dephosphorylation involves protein phosphatases 2A and 2B in SH-SY5Y human neuroblastoma cells
- Lee, Yun-Il; Seo, MiRan; Kim, Yeni; Kim, So-Young; Kang, Ung Gu; Kim, Yong-Sik; Juhnn, Yong-Sung
- Issue Date
- J Biol Chem. 280(23), 22044-22052
- Androstadienes/pharmacology; Animals; Calcineurin/*chemistry; Calcium/metabolism; Cell Line; Cell Line, Tumor; Cell Membrane/*metabolism; Enzyme Inhibitors/pharmacology; Glioblastoma/metabolism; Glycogen Synthase Kinase 3/*metabolism; Hippocampus/cytology/metabolism; Humans; Immunoblotting; Immunoprecipitation; Microscopy, Confocal; Naphthalenes/pharmacology; PC12 Cells; Phosphoprotein Phosphatases/*chemistry; Phosphorylation; Potassium Chloride/pharmacology; Rats; Serine/chemistry; Threonine/chemistry; Time Factors; Transfection
- Changes in plasma membrane electrical potential evoke signals that regulate the expressions of various genes in the nervous system. However, the role of glycogen synthase kinase 3beta (GSK-3beta) in this process has not been elucidated. Thus, this study was performed to examine whether membrane depolarization can regulate the phosphorylation of GSK-3beta and to identify the molecular mechanisms involved in this regulation. The depolarization by treating with 100 mm KCl for 5 min resulted in the undulating phosphorylation of GSK-3beta at Ser-9 in SH-SY5Y human neuroblastoma cells, in H19 -7/IGF-IR rat embryonic hippocampal cells, and in PC12 rat pheochromocytoma cells, but not in A172 human glioblastoma cells. Cellular beta-catenin contents showed a temporal pattern similar to that of the Ser-9 phosphorylation of GSK-3beta. Treatment with wortmannin or calphostin C or the expression of dominant negative Akt inhibited phosphorylation of GSK-3beta at Ser-9 following the KCl-induced depolarization of SH-SY5Y cells. Moreover, pretreatment with okadaic acid or cyclosporin A blocked the dephosphorylation of GSK-3beta at Ser-9 at 0, 15, and 30 min after KCl-induced depolarization, and the activity of protein phosphatases (PP) 2A and 2B increased at these times. Treatment with nifedipine or calcium-free medium inhibited GSK-3beta dephosphorylation following membrane depolarization, and the amounts of co-immunoprecipitated GSK-3beta and PP2A changed in parallel with GSK-3beta dephosphorylation. Our study demonstrated that KCl-induced depolarization caused undulating GSK-3beta phosphorylation/dephosphorylation, which was regulated for the most part by phosphatidylinositol 3-kinase and Akt (phosphorylation) and PP2A and PP2B (dephosphorylation), respectively.
- 0021-9258 (Print)
- Files in This Item: There are no files associated with this item.